Protein** C inhibitor** (PCI, SERPINA5) is a ser****ine protease inhibitor (serpin) that limits the activity of protein C (an anticoagulant). An N-terminal fragment of PCI is a possible serum biomarker for prostate cancer. Protein C inhibitor is activated by heparin against thrombin. Protein C inhibitor (PCI) is serine protease inhibitor of serpin type that is found in most tissues and fluids, including blood plasma, seminal plasma and urine of human. It is a 52kD glycoprotein and belongs to serine protease inhibitor ( Serpin) super family of protein. In the beginning protein C Inhibitor (PCI) was identified as an inhibitor of activated protein C (APC), it is currently clear that this inhibitor has an expansive specificity, inhibiting several blood coagulation enzymes counting thrombin and factor Xa.

Isolation

In the beginning, protein C inhibitor(PCI) was originally identified in human plasma by Griffin and Marlar and first isolation was performed by Suzuki et al. Protein C inhibitor (PCI) can be isolated from human plasma using an ordinary chromatographic procedure consisting of barium citrate adsorption, polyethylene glycol fractionation, DEAE-Sepharose CL-6B treatment, ammonium sulfate fractionation, dextran sulfate-agarose chromatography, gel filtration on ACA-44, and DEAE-Sephacel chromatography.

Structure

The structure (primary structure) of protein C inhibitor was deduced from its cDNA nucleotide sequence. The human Protein C inhibitor have 19 amino acid signal peptide.

Gene organization

The study of genomic DNA by restriction mapping, polymerase chain reaction analysis and DNA sequencing showed the gene being 11.5 kilobases in length, consisting of five exons separated by four introns. The genetic code of protein C inhibitor is similar to alpha 1-antitrypsin and alpha 1-antichymotrypsin.

Metabolism

The in vivo half time degradation of protein C inhibitor in plasma is found to be 23 hours, whereas the half time degradation of protein C inhibitor and protein C complex is 20 minutes.

Binding with heparin

Protein C inhibitors have ability to inhibit protein C, thrombin and other enzymes that are stimulated by heparin. The heparin binding site of protein C inhibitor is from 264-283 region. Heparin enhances the rate of inhibition leading to the conformational change in the structure of Protein C and other proteases. The binding site of heparin is different for protein C inhibitor and other proteases Heparin regulates the protein C inhibitor (PCI) activity and furthermore its specificity in those system where there is presence of two or more target proteases.

Clinical significance

As an antimicrobial agent

Protein C inhibitor interacts with lipid membrane subsequently leading to permeabilization of bacterial pathogen exerting the antimicrobial activity. Protein C inhibitor a potent antimicrobial agent that have ability to destroy the bacterial cell wall, causing death of the bacteria.

Reproduction

Protein C inhibitor significantly reduces fertilization by inhibiting both the binding and penetration of zona free hamster oocytes by human sperm. This effect of PCI is dose dependent as 0.04MicroM PCI inhibited 50% binding and penetration ability.

Inhibition of tumor growth

PCI communicated by malignant cells smothers tumor invasion by hindering urokinase-sort plasminogen activator, and restrains tumor development and metastasis which is independent of its protease inhibitory activity.

Deficiency

Deficiency of protein C inhibitor in the human body may cause male infertility. Protein C inhibitor has a role in reproduction as it has ability to inhibit the sperm protease acrosin. Large amounts of protein C inhibitor circulate in the male reproductive organ as a plasma protein. Either deficiency or the presence of inactive protein C inhibitor can lead to male caused infertility.

Interactions

Protein C inhibitor has often been shown to interact with prostate specific antigen, protein C and PLAU.